Yusuke Nakauchi M.D., Ph.D.

Postdoctoral Research fellow, Stanford Cancer Center

Bio

My research projects aim to investigate the biology of human acute myeloid leukemia (especially on leukemic stem cell). I believe my research will contribute to clarify the disease pathogenesis of leukemia that leads to overcome the disease.

Honors & Awards

Overseas Award, Nakayama Foundation for Human Science (2014)

Professional Education

Doctor of Philosophy, The University of Tokyo, Stem Cell Biology (2014)

Abstract

Graft-versus-host disease (GVHD), mediated by donor-derived alloreactive T cells, is a major cause of non-relapse mortality in allogeneic hematopoietic stem-cell transplantation (allo-HSCT). Its therapy is not well-defined. We established allele-specific anti-HLA monoclonal antibodies (ASHmAbs) that specifically target HLA molecules, with steady death of target-expressing cells. One such ASHmAb, against HLA-A*02:01 (A2-kASHmAb), was examined in a xenogeneic GVHD mouse model. To induce fatal GVHD, non-irradiated NOD/Shi-scid/IL-2Rγ(null) (NOG) mice were injected with healthy-donor human peripheral blood mononuclear cells (PBMCs), some expressing HLA-A*02:01, some not. Administration of A2-kASHmAb promoted the survival of mice injected with HLA-A*02:01-expressing PBMCs (p<0.0001) and, in humanized NOG mice, immediately cleared HLA-A*02:01-expressing human blood cells from mouse peripheral blood. Human PBMCs were again detectable in mouse blood 2-4 weeks after A2-kASHmAb administration, suggesting that kASHmAb may be safely administered to GVHD patients without permanently ablating the graft. This approach, different from those of existing GVHD pharmacotherapy, may open a new door for treatment of GVHD in HLA-mismatched allo-HSCT.

Abstract

Intraocular lymphoma (IOL) is rare lymphoma that frequently infiltrates the central nervous system (CNS). An optimal treatment has not been established, and its prognosis is quite poor. We treated three IOL patients with CNS involvement by concurrent administration of intravenous and intravitreal methotrexate (MTX) injection. The intraocular lesion responded in all patients. One patient achieved complete response (CR), whereas the other 2 patients were in partial response for CNS lesion, added whole brain radiation and achieved CR. In 3 eyes of 2 patients, an intravitreal MTX injection (vMTX) was administered 2 h after a systemic MTX injection (sMTX) and the intravitreal MTX concentration was measured twice: 2 h after sMTX and 24 h after vMTX. The half-life of MTX in the vitreous fluid was estimated to be 12.4-21.5 h by assuming the first-order elimination kinetics. Although the concentration was still high 24 h after vMTX (69.94-82.89 muM), there were no ocular complications. The serum MTX concentration was not influenced by adding vMTX to sMTX. Grade 3 adverse event, leukocytopenia, was observed in only 1 patient. No grade 4 event was observed. Although further evaluation is required, concurrent sMTX and vMTX may be effective for IOL with CNS involvement.